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GWAS of Psoriasis and Psoriatic Arthritis
Psoriasis Overview Psoriasis is a chronic autoimmune disease that is caused by the immune system T cells attacking normal skin cells. This leads to increased blood flow and white blood cells to the skin area as well as an overproduction of new skin cells (1). Therefore the most common symptoms associated with psoriasis include raised red scaly patches to appear on the skin surface (2). The red patches can appear pretty much anywhere on the body but common areas include around the elbows, knees, scalp, lower back, face, feet and nails (2). The most common complaints regarding psoriasis include an itching or burning around the inflammed area as well as a particularly unpleasant appearance. There are varying degrees of severity concurrent with psoraisis as well as 5 different types of the disease: Plaque Psoriasis: This form of psoriasis consists of raised red patches surrounded by characteristic whitish scales (dead skin cells). This is the most common form of psoriasis and is found frequently around the knees elbows, scalp, and lower back (2). Guttate: This form of psoriasis starts in children most frequently and accounts for about 10% of psoriasis cases (2). Inverse: This form of psoriasis has characteristically large, smooth shiny red areas that normally occur in joint folds such as knees and elbows (2). Pustular: This form of psoriasis contains white blisters (pustules of white blood cells) surrounded by red skin (2). Erythrodermic: This form of psoriasis covers most of the skin surface of the body and is characterized by redness and skin exfoliation but is very rare (2). Psoriatic Arthritis Psoriatic Arthritis occurs in about 30% of people with psoriasis (2). This disease normally affects joints that are closest to the nail in the fingers and toes. Symptoms are similar to rheumatoid arthritis and consist of varying degrees of progressive joint damage. Some common symptoms associated with psoriatic arthritis are tendonitis and bursitis, swollen fingers and toes (dactylitis), stiffness, swelling, and pain of the affected joints (2). Genome-Wide Association Study This genome-wide associated study was performed to identify genetic markers that indicated increases susceptibility to psoriasis and psoriatic arthritis (3). For this study 223 psoriasis patients (with 91 of them also diagnosed with psoriatic arthritis) were genotyped using the Illumina HumanHap300 arrays. Their sequences were then compared to a control group of 519 people without the diseases using the same genotyping process (3). These groups were all specifically genotyped with 311,398 SNPs and compared to eachother to conclude differences. Results indicated and supported other GWAS studies of these diseases that the strongest association to the disease were found within the region of the genome that coded for the major histocompatibility complex 1 (MHC-1) and the most commonly associated SNP was found upstream of that gene at position rs10484554 (3). Another genes that had varying SNPs that were associated with the diseases were found in the interleukin 2 receptor and interleukin 12B specifically found at position rs11209036 and position rs6887695 respectively (3). New polymorphism associations were also found witin this study as well at various positions within the genomes at: -Chromosome13q13 a SNP at position rs7993214 within the COG6 gene (coding for part of the oligomeric golgi complex component 6)(3). -Chromosome 15q21 a SNP at position rs3803369 which codes for ubiquitin-specific protease-8 (which lies upstream from the HLA-C gene). This was of great interest because this area also encodes the SPPL2a gene which functions to activate tumor necrosis alpha factor which leads to expression of interleukins (3). -Chromosom 4q27 contained various SNPs associated with the diseases as well. This area codes for interleukin 2 and interleukin 21 (3). References 1. "Psoriasis." Wikipedia. Wikimedia Foundation 2. "About Psoriasis." National Psoriasis Foundation. National Psoriasis Foundation, 2014. 3. Lui, Y. "A Genome-wide Association Study of Psoriasis and Psoriatic Arthritis Identifies New Disease Loci." National Center for Biotechnology Information. U.S. National Library of Medicine, 28 Mar. 2008. Pubmed ID: 18369459